tbuckley/cabot-search huggingface dataset:
Tepotinib in Asian patients with advanced NSCLC with <i>MET</i> exon 14 (<i>MET</i>ex14) skipping.
Authors: Terufumi Kato, James Chih-Hsin Yang, Myung-Ju Ahn, Hiroshi Sakai, Masahiro Morise, Yuh-Min Chen, Ji-Youn Han, Jin-Ji Yang, Jun Zhao, Jason Huang, Karin Berghoff, Rolf Bruns, Helene Vioix, Gordon Otto, Xiuning Le, Paul K. Paik
Journal: Journal of Clinical Oncology (2022)

9120 Background: Tepotinib is a highly selective, potent MET inhibitor approved in several Asian countries for the treatment of advanced METex14 skipping NSCLC. In VISION (n=275; data cut-off: Feb 1, 2021), tepotinib had an objective response rate (ORR) of 49.1% (95% CI: 43.0, 55.2) by independent review (IRC), with a median (m) DOR of 13.8 months (9.9, 19.4) across treatment lines. Here, we report outcomes in Asian pts. Methods: Pts with advanced METex14 skipping NSCLC, detected by liquid (L+) or tissue (T+) biopsy, received tepotinib 500 mg (450 mg active moiety) QD. Primary endpoint was objective response by IRC. Efficacy was assessed in 79 Asian pts with ≥3 months’ follow-up, and safety was assessed in 88 Asian pts who received tepotinib by data cut-off (Feb 1, 2021). Only pts enrolled in Asia were assessed for HRQoL. Results: In 79 Asian pts assessed for efficacy (38% female, 42% smoking history, 34% treatment-naïve [1L] and 82% adenocarcinoma), ORR was 54.4% (42.8, 65.7), mDOR was 18.5 months (8.3, ne), mPFS was 12.1 months (6.9, ne) and mOS was 20.4 months (19.1, ne). ORR was 66.7% (46.0, 83.5) in 1L pts (n=27), and 48.1% (34.0, 62.4) in previously treated pts (n=52). Meaningful activity was observed irrespective of METex14 skipping detection method (Table). In pts analyzed for HRQoL (n=73), mean change from baseline for EORTC QLQ-C30 GHS (3.94), EQ-5D-5L VAS (0.83), and EORTC QLQ-LC13 for cough (-6.59), dyspnea (-1.26), and chest pain (-6.14) symptom scores, demonstrated stability in QoL. In 88 Asian pts analyzed for safety, the most common adverse events (AEs) were peripheral edema, increased blood creatinine, and diarrhea. 29.5% of pts had Grade ≥3 treatment-related (TR) AEs. TRAEs led to dose reductions in 29.5%, temporary interruption in 43.2%, and permanent discontinuation in 14.8% of pts. Conclusions: In VISION, tepotinib showed robust and durable clinical activity in Asian pts with METex14 skipping NSCLC. TRAEs were manageable, with few leading to treatment discontinuation. Currently, VISION has enrolled 106 Asian pts with METex14 skipping NSCLC; analysis in this population is ongoing. Clinical trial information: NCT02864992. [Table: see text]
Necroptosis-related lncRNA biomarkers for colon cancer prognosis and the associations with the immune landscape.
Authors: Tao Wang, Shaohua Xu, Qian Wang, Shanshan Xiao
Journal: Journal of Clinical Oncology (2022)

e15525 Background: Necroptosis is a regulated caspases-independent cell death involved in colon cancer development and antitumor activity. lncRNAs are widely considered as biomarkers in various diseases. In this study, we identified prognosis biomarkers using necroptosis-related lncRNAs, and predict immunotherapeutic responses for colon cancer. Methods: A total of 453 colon cancer (CRC) patients (480 normal and 41 tumor samples) were enrolled in this study. The RNA expression dataset were obtained from The Cancer Genome Atlas (TCGA-COAD). They were randomly grouped as training set and validation set(7:3 ratio). Necroptosis-related lncRNAs were identified using Pearson’s correlation analysis with 67 necroptosis-related genes previously reported. Stepwise Cox regression and LASSO algorithm were performed to construct the prognostic risk score model. The overall survival (OS) difference between the high- and low-risk groups(cutoff using median risk score) was compared using Kaplan-Meier statistics. Furthermore, we evaluated the associations between the identified lncRNAs and the immune-related phenotypes including tumor micro-environment (TME) scores calculated by ESTIMATE, immune cell infiltration estimated by CIBERSORT, chemotherapeutics sensitivity predicted by pRRophetic and immune checkpoint expression,etc. Results: A total of 1926 necroptosis-related lncRNAs were identified and four lncRNAs (LINC02753, AC073283, AC010973, AP003555) were found to be correlated with 10 differential expressed necroptosis-related genes. The identified four lncRNAs were used to construct the prognostic model. The identified biomarkers was found to significantly correlate with worse prognosis in TCGA cohort (Train set: HR = 4.65, 95%CI = 2.42-8.93, P &lt; 0.001; Validation set: HR = 3.06, 95%CI = 1.32-7.12, P = 0.006; Whole set: HR = 4.04, 95%CI = 2.41-6.76, P &lt; 0.001) and was found to be independent to clinicopathological parameters. In addition, the lower TME scores suggested the lower infiltration of non-tumor cells in high-risk group and eight drugs were predicted to be more effective in high-risk group (i.e., PAC-1, AS601245). Further immune-related analysis revealed that the infiltrating immune cells including B cells, CD4 T cells, resting NK cells, M1 macrophages, monocytes, were all significantly different between the two groups. Moreover, TNF superfamily members (i.e., TNFSF14/15/25) were found to be substantially increased in high-risk group, which was considered as a type of important immune checkpoint molecule and participates in the initiation and regulation of necroptosis. Conclusions: The identified 4-lncRNA signature based on necroptosis showed potential prognosis value in CRC patients. The results can also help to guide immunotherapy and clinical research with TNFSF inhibitors for colon cancer patients with further experimental and clinical validation.
Economic impact of digital tumor board software: An evaluation of cost savings using real-world data.
Authors: Richard D. Hammer, Sharan Srinivas, Suchithra Rajendran, Chaohui Guo, Matthew Stewart Prime
Journal: Journal of Clinical Oncology (2022)

e18794 Background: Multidisciplinary tumor boards (MTB) provide an interdisciplinary approach for decision-making in cancer care and are an integral part of cancer treatment plans. MTBs are widely considered the “gold standard” in cancer care delivery and are required for accreditation by the American College of Surgeons on Cancer Program. Preparing for MTBs is time-consuming and labor-intensive. We have previously published the largest real-world study of a digital solution (NAVIFY), showing significant decreases in the case preparation time compared to traditional methods. 1 We now extend that study to evaluate the economic impact on costs of MTBs in an academic setting. Methods: The NAVIFY Tumor Board solution was introduced at the University of Missouri Health Care (MU) in 2018. Data was collected in three tumor boards (Breast, ENT, and GI) for pre- and post- NAVIFY implementation as previously published 1 . For the current study, raw data was collected and preprocessed to obtain eight pertinent variables. A retrospective pre-post analysis was used to evaluate the economic effectiveness of NAVIFY. Using the salary data collected from publicly available sources, the average personnel cost/case (nurse navigator, radiology, pathology and genetic counseling) was analyzed for each tumor board for pre and post stable integration of NAVIFY. In addition, a system-wide cost projection study and payback analysis were also performed based on 12 tumor boards. Results: The average personnel cost/case after integration of NAVIFY showed a savings of 40% in breast MTB, 52% for ENT MTB, and 6% for GI MTB. Both Breast and ENT were considered to be the optimal use of the software after implementation. Using these two tumor boards, the average total personnel cost/case pre-NAVIFY was $93.20 and $49.55 post integration. Annual system-wide cost projections showed an annual savings of $299,614. Discounted payback period analysis showed a payback period of 0.17 years. Conclusions: Implementation of NAVIFY digital tumor board solution showed a significant impact on the total cost of tumor board preparation with overall a decrease in personnel cost/case of 53% with ideal implementation. The comparatively slight decrease in GI could be explained by an increase in cases reviewed from an average of 8 to 11 pre vs post NAVIFY requiring increased radiologist time, and poor user adoption by surgeons. In conclusion, implementation of a digital tumor board software provides significant savings in case preparation costs, second to decreased time costs of personnel. While not evaluated in this study, these cost savings do not take into account the increased potential clinical revenue that may also accompany the improved efficiency on provider time. References 1. Hammer RD, etal. Digital Tumor Board Solutions Have Significant Impact on Case Preparation. JCO Clin Cancer Inform. 2020 Aug;4:757-768.
Does race influence long-term outcomes after neoadjuvant chemotherapy in breast cancer: A National Cancer Database analysis.
Authors: Arya Mariam Roy, Changchuan Jiang, Song Yao, Stuthi Perimbeti, Shipra Gandhi
Journal: Journal of Clinical Oncology (2022)

606 Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a surrogate predictor for long-term survival in breast cancer (BC). Patients who attain pCR have improved relapse-free and overall survival (OS) when compared to patients with residual disease (RD). We examined the pCR in Black and White BC patients who received NACT and their OS after attaining pCR and RD. Methods: The National Cancer Database (NCDB) was queried for Black and White females with non-metastatic BC from the years 2010 – 2016 who received NACT. Logistic regression was used to analyze pCR/RD and Cox proportional hazards regression to analyze OS, with adjustment for age, race, stage, grade, body mass index, treatments received, insurance status and comorbidities. STATA/IC 16.0 was used for analysis and a two-sided p-value &lt; 0.05 was considered significant. Results: A total of 101,014 White and Black BC patients were identified, including 24,852 (Whites - 74.43%, Black - 25.57%) triple negative breast cancer (TNBC), 51,043 (Whites - 84%, Blacks - 16%) hormone receptor positive HER2 negative (HR+HER2-) and 17,818 (Whites - 83%, Blacks - 17%) HER2 positive. Whites had a slightly higher odds of attaining pCR compared to Blacks (adjusted Odds Ratio (aOR) = 1.040, 95% Confidence Interval (CI) = 1.02 - 1.19, p = 0.02). The difference was largest in TNBC subtype (TNBC: aOR = 1.34, 95% CI = 1.20 - 1.56, p &lt; 0.001; HR+HER2-: aOR = 1.1; 95% CI = 1.02 - 1.32, p = 0.038; HER2+: aOR = 1.13, 95% CI = 1.08 - 1.27, p &lt; 0.001). Among those who attained pCR, Blacks had worse OS when compared to Whites in HER2+ subtype (adjusted Hazard Ratio (aHR) = 1.41, 95% CI = 1.04 - 1.93, p = 0.028) but not in TNBC or HR+HER2- subtypes. Among those with RD, Blacks had worse OS in the whole cohort compared to Whites (aHR = 1.43, 95% CI = 1.26 - 1.58, p &lt; 0.001), and in all subtypes: TNBC (aHR = 1.17, 95% CI = 1.11 - 1.23, p &lt; 0.001), HR+HER2- (aHR = 1.38, 95% CI = 1.31 - 1.45, p &lt; 0.001) and HER2+ (aHR = 1.45, 95% CI = 1.32 - 1.59, p &lt; 0.001). Conclusions: Black BC patients with TNBC were less likely to achieve pCR than Whites after NACT. When Black patients with HER2+ subtype did attain pCR, they still had worse OS than Whites. The same racial difference in OS was observed in all BC subtypes - TNBC, HR+HER2- and HER2+ among patients with RD. This highlights the importance to investigate novel personalized treatment strategies for Black patients.
Global, Regional, and National Incidence and Mortality of Neonatal Preterm Birth, 1990-2019
Authors: Guiying Cao, Jue Liu, Min Liu
Journal: JAMA Pediatrics (2022)

<h3>Importance</h3> Preterm birth complications are the leading cause of death in children younger than 5 years worldwide. Despite advancing knowledge of risk factors and mechanisms related to preterm labor, the preterm birth rate has risen in most industrialized countries. Moreover, the burden of neonatal preterm birth remains unclear across the world. <h3>Objective</h3> To determine the trends in incidence and mortality of neonatal preterm birth at the global, regional, and national levels to quantify its burden from 1990 to 2019 using data from the 2019 Global Burden of Disease study. <h3>Design, Setting, and Participants</h3> Annual incident cases, deaths, age-standardized incidence rates (ASIRs), and age-standardized mortality rates (ASMRs) of neonatal preterm birth between 1990 and 2019 were collected from the 2019 Global Burden of Disease study. The percentage of relative changes in incident cases and deaths as well as the estimated annual percentage changes (EAPCs) of ASIRs and ASMRs were calculated to quantify their temporal trends. Correlations of EAPC of ASIRs and ASMRs with sociodemographic index (SDI) and universal health coverage index were evaluated by Pearson correlation analyses. <h3>Exposures</h3> Infants born alive before 37 completed weeks of gestation between 1990 and 2019. <h3>Main Outcomes and Measures</h3> Incident cases, deaths, ASIRs, and ASMRs of neonatal preterm birth. <h3>Results</h3> Globally, the incident cases of neonatal preterm birth decreased by 5.26% from 16.06 million in 1990 to 15.22 million in 2019, and the deaths decreased by 47.71% from 1.27 million in 1990 to 0.66 million in 2019. The overall ASIR (EAPC = −0.19 [95% CI, −0.27 to −0.11]) and ASMR (EAPC = −2.09 [95% CI, −1.99 to −2.20]) decreased in this period. The ASIR of neonatal preterm birth increased by a mean of 0.25% (95% CI, 0.13%-0.38%) in high-SDI regions from 1990 to 2019. The ASMR of neonatal preterm birth increased by a mean of 2.09% (95% CI, 1.99%-2.20%) in Southern Sub-Saharan Africa in this period. A positive correlation was observed between EAPC of ASIR and SDI or universal health coverage index in 2019, while a negative correlation was observed between EAPC in ASMR and SDI or universal health coverage index in 2019 at national levels. <h3>Conclusions and Relevance</h3> Preterm birth remains a crucial issue in children worldwide, with an increasing trend in ASIR in high-SDI regions and in ASMR in Southern Sub-Saharan Africa between 1990 to 2019. Efforts to reduce both the incidence and mortality of preterm births are essential.
Management of Patients With Advanced Melanoma
Authors: Genevieve Boland
Journal: Journal of the National Comprehensive Cancer Network (2022)

For treatment of melanoma, accumulated research has allowed the transition of the most effective treatments into earlier stages of disease management. To this end, immunotherapy has become approved for high-risk stage II and resected stage III melanoma, and is currently being evaluated in the neoadjuvant setting. BRAF/MEK-targeted therapy is also approved in the adjuvant setting and is being evaluated in neoadjuvant trials. In stage IV disease, the optimal sequencing of these 2 main approaches is with immunotherapy initiated first. Recently, the LAG-3 antibody relatlimab, in combination with nivolumab, has produced impressive responses with low toxicity and has become a new standard of care compared with anti–PD-1 monotherapy. As heterogeneity within disease stages has become better appreciated, staging and risk classification have been refined.
Brain Tumor Cell Membrane‐Coated Lanthanide‐Doped Nanoparticles for NIR‐IIb Luminescence Imaging and Surgical Navigation of Glioma
Authors: Zijun Wang, Meng Zhang, Siyu Chi, Mengting Zhu, Caixia Wang, Zhihong Liu
Journal: Advanced Healthcare Materials (2022)

Intraoperative visualization of the full extent of brain tumor by luminescence imaging helps to improve the degree and accuracy of brain tumor resection, thereby prolonging the survival of patients. However, the limited imaging depth and spatial resolution and the poor blood-brain barrier (BBB) permeability of most currently available luminescent probes restrict the imaging performance and surgical resection efficiency of brain tumor. Here, a brain tumor cell membrane-coated lanthanide-doped nanoparticles (CC-LnNPs) in the near-infrared-IIb window (NIR-IIb, 1500-1700 nm) is designed for brain tumor imaging and surgical navigation. The coating of brain tumor cell membrane endows CC-LnNPs with immune escape, BBB crossing, and homotypic targeting abilities, which are inherited from the source brain tumor cells. In addition, compared with clinically approved imaging agent indocyanine green, CC-LnNPs present higher temporal and spatial resolution, higher stability, and lower background signals, enabling clear visualization of the brain tumor boundary. With the guidance of NIR-IIb fluorescence, the glioma tissue (size < 3 mm, depth > 3 mm) could be clearly visualized and completely removed as a proof of concept. This study offers new insight for the future design of nanoprobe to image brain tumor and to achieve precise diagnosis and surgical navigation of brain tumor.
Cross-sectional associations between the gut microbe Ruminococcus gnavus and features of the metabolic syndrome: the HUNT study
Authors: Louise Grahnemo, Maria Nethander, Eivind Coward, Maiken Elvestad Gabrielsen, Satya Sree, Jean-Marc Billod, Lars Engstrand, Sanna Abrahamsson, Arnulf Langhammer, Kristian Hveem, Claes Ohlsson
Journal: The Lancet Diabetes & Endocrinology (2022)
Diagnosis of first relapse and its impact on quality of life in patients with advanced ovarian cancer (AGO-OVAR 19/II).
Authors: Philipp Harter, Beyhan Ataseven, Alexander Burges, Alexander Reuss, Stefan Kommoss, Jalid Sehouli, Bjoern Lampe, Barbara Schmalfeldt, Pauline Wimberger, Ralf Witteler, Paul Buderath, Uwe Herwig, Holger Bronger, Guenter Emons, Maximillian Klar, Annette Hasenburg, Nikolaus de Gregorio, Felix Hilpert, Andreas Du Bois, Sven Mahner
Journal: Journal of Clinical Oncology (2022)

e17609 Background: Maintenance or improvement of health-related quality of life (QoL) is one of the major goals for patients with advanced ovarian cancer (OC). QoL is influenced by symptoms of disease on the one and beneficial or adverse effects of surgical and systemic treatment on the other side. In addition, QoL is also an important patient centered endpoint in clinical trials to support primary endpoints such as progression-free survival (PFS). This analysis evaluates the impact of the diagnosis of first relapse on QoL. Methods: Patients with primary OC were included before start of treatment. QoL was assessed by the cancer-specific questionnaires EORTC QLQ‐C30 and QLQ‐OV28 and the generic EQ‐5D 3L at baseline and every 3 months thereafter, to describe the influence of treatment and course of disease on QoL. QoL data within 100 days before and after the first relapse were compared (part 2 of NCT02828618). QoL scales were analyzed by repeated measures regression. We report model-based pre- and post-recurrence means and p-values for the difference in means. Results: In total, 269 had a PFS event with a median PFS of 20.3 months. This analysis includes 186 patients; 122 with QoL assessment before and after relapse and 50 and 14 with assessment only before or after relapse. Median age was 62.5 years (range 31 – 90). The number of evaluable answers for each domain ranged between 166 and 172 before recurrence and 135 and 137 after recurrence. Global QoL decreased from 61.4 to 48.4 points (p &lt; 0.001) with the diagnosis of recurrence. The following scales showed a deterioration of at least 10 points: Social functioning (65.7- &gt; 52.6), fatigue (55.8 - &gt; 44.5), appetite loss (22.5 - &gt; 33.4), emotional functioning (65.2 - &gt; 54.9), role functioning (56.5 - &gt; 46.4); (all p &lt; 0.001). EQ-5D 3L visual analogue scale showed a deterioration from 66.4 to 55.0 (p &lt; 0.001). Conclusions: The event of first relapse is associated with a significant and clinically relevant deterioration of global QoL including several subscales. Therefore, prolongation of PFS preserves QoL, which supports the role of PFS as meaningful primary endpoint in ovarian cancer trials. Clinical trial information: NCT02828618.
ETMR-03. Intra- and extra-cranial BCOR-ITD tumours are separate entities within the BCOR-rearranged family
Authors: Yassine Bouchoucha, Arnault Tauziède-Espariat, Arnaud Gauthier, Delphine Guillemot, Dorian Bochaton, Julien Vibert, Matthieur Carton, Sarah Watson, Sandrine Grossetete, Chloé Quignot, Daniel Orbach, Nadège Corradini, Gudrun Schleiermacher, Franck Bourdeaut, Marie Simbozel, Christelle Dufour, Veronique Minard, Mehdi Brahmi, Franck Tirode, Daniel Pissaloux, Marie Karanian, Marie-Christine Machet, Julien Masliah-Planchon, Olivier Delattre, Liesbeth Cardoen, Gaelle Pierron, Francois Doz
Journal: Neuro-Oncology (2022)

Abstract BCOR-ITD tumours form an emerging family of aggressive entities with an internal tandem duplication (ITD) in the last exon of the BCOR gene. The family includes cerebral tumours, termed central nervous system BCOR-ITD (CNS BCOR-ITD), and sarcomatous types described in the kidney as clear cell sarcoma of the kidney (CCSK), in the endometrium as high-grade endometrial stromal sarcoma (HG-ESS), in bone, and in soft tissue as undifferentiated round cell sarcoma (URCS) or primitive myxoid mesenchymal tumour of infancy (PMMTI). Based on a series of 33 retrospective cases, including 10 CNS BCOR-ITD and 23 BCOR-ITD sarcomas, we interrogated the homogeneity of the entity regarding clinical, radiological and histopathological findings, and molecular signatures. Whole transcriptomic sequencing and DNA methylation profiling were used for unsupervised clustering. Histopathological review revealed marked differences between CNS BCOR-ITD and BCOR-ITD sarcomas. These two groups were consistently segregated by unsupervised clustering of expression (n=22) and DNA methylation (n=21) data. Proximity between the two groups may result from common somatic changes within key pathways directly related to the novel activity of the ITD itself. Conversely, comparison of gene signatures with single-cell RNAseq atlases suggests that the distinction between BCOR-ITD sarcomas and CNS BCOR-ITD may result from differences in cells of origin.
Complement C5 plasma levels are associated to abdominal aortic aneurysm prevalence and progression
Authors: D Martinez-Lopez, N Mendez-Barbero, R Roldan-Montero, I Cerro-Pardo, B Picatoste, L Ortega-Villanueva, S Rodriguez De Cordoba, LM Blanco-Colio, JS Linhdolt, JL Martin-Ventura
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Complemento II-CM La Caixa Aim Previous human and experimental studies have suggested a role of complement activation in abdominal aortic aneurysm (AAA). We recently described an increase in complement C5 levels in plasma of subjects with subclinical atherosclerosis (1). Our aim was to investigate the potential association of C5 with AAA presence and progression. Material and methods Tissue and tissue-conditioned media from AAA (thrombus and wall) or healthy samples were obtained from surgical repair or brain-deceased organ donors, respectively. Blood samples from 490 AAA patients (maximal aortic diameter ≥30 mm) were obtained within a population-based ultrasound-screening trial in Danish men and from 176 age-matched screened negative controls. C5 protein levels were assessed by immunohistochemistry and ELISA. Results High C5 positive immunostaining was observed in AAA thrombus and media, while the staining in healthy arteries was faint. C5 levels were higher in tissue-conditioned media from AAA thrombus and AAA media as compared to healthy arteries (7.1±1 vs 2.9 ±0.5 vs 1.2±0.2ug/ml, p&amp;lt;0.0001 for both). C5 plasma levels in AAA patients were higher than in controls (116±8 vs 61±7 ug/ml, P&amp;lt;0.001). AAA patients at the upper tertile of C5 at baseline had a 25% higher risk of needing surgical repair during the follow-up (Hazard Ratio=1.25, 95% confidence interval, 1.045;1.511, P&amp;lt;0.05). Conclusions C5 is associated to AAA presence and progression suggesting its potential use as a prognostic marker. Future studies are needed to clarify the pathogenic role of C5 in AAA.